and and colleagues at the University of Leeds used electrodes instead of conventional glass slides to make their device.

The electrodes are only about 10 micrometers apart and could ultimately be made even smaller, they say.

Existing sensors use antibodies that bind to target proteins. But antibodies are unstable and become poorer at identifying disease proteins when attached to components within a sensor.

At present, scientists must also label proteins with fluorescent tags and then use optical techniques to detect them – a process that looks at just one protein at a time and is both complex and imprecise.

Instant result

“We wanted to short-circuit that,” says . “So in real time a clinician might be able to take a sample, mush it up and put it over an electrode array and say immediately that a cancer is present and what the origin of that cancer might be.”

The team created peptide aptamers – artificial antibodies that are very stable and bind easily to a specific proteins – and attached them to their microscopic electrodes. When a target protein binds to an aptamer, the electrodes generate an electronic signal, immediately indicating the presence of the protein.

To test the effectiveness of the device, the team exposed an array of electrodes – each with one of two different peptide aptamers attached – to a mixture made from broken down, or “lysate”, yeast cells, which has similar complexity to blood or urine.

Multiple protein test

One set of electrodes carried aptamers with an affinity for a particular protein found in the mixture. When dipped into the mixture, these electrodes lit up to signal the presence of the proteins.

The device can be manufactured using technology already commonplace in the microchip industry, so the team says it should be simple to increase the number of sensors involved and to scale the device down further.

“Using semiconductor technology provides huge advantages,” says Davies.

This offers the possibility of a device capable of identifying multiple proteins simultaneously, and even analysing multiple protein interactions at the level of a single cell, the authors claim.

Journal reference: (DOI: 10.1186/jbiol62)

And catch-up growth during childhood does not change this, say the researchers.

This is in contrast to other research which suggests that once short babies achieve normal height, their risk of schizophrenia, lower cognitive function and other mental health problems decreases.

“But this was not true for suicide attempts,” says , at the Karolinska Institute in Stockholm, who led the study.

The team followed up 318,953 men born in Sweden between 1973 and 1980 until their first suicide attempt, death, emigration, or the end of 1999.

Womb link

Violent deaths were defined as hanging, shooting, cutting, jumping from height or in front of a moving vehicle, drowning, or intentionally crashing.

The team found both that males born measuring less than 47 centimetres, and those of low birth weight (below 2.5 kilograms or 5.5 pounds) presented a similar risk of a violent suicide attempt. Whilst being born preterm (before 34 weeks) increased the risk over four-fold.

Being born normal length (51 to 52 cm) but remaining short as an adult increased the risk of attempting suicide by 56%. The taller a man was, the less likely it was that he would attempt suicide.

Mittendorfer-Rutz says the research shows that violent suicide attempts were more strongly linked to the period in-utero than non-violent attempts.

“We know that serotonin metabolism is linked to depression and suicidal behaviour,” she says. “It could be a link with prenatal exposure or it could be the effect of any kind of stress on serotonin metabolism.”

Early effects

Such stresses might be maternal alcohol, drug abuse, or smoking during pregnancy that can lead to fetal growth restriction or preterm birth and so increase their child’s risk of suicidal behaviour and mental disorders later on, she adds.

The effects of short stature on health have been documented previously. In 2000, Robin Dunbar, an evolutionary anthropologist at University of Oxford, UK, showed that tall men were more likely to marry and have children than shorter men.

It has also been shown that women find tallness attractive, and studies have shown that stature correlates with income in men, but not women.

“This seems to suggest that small body-size effects start very early,” says Dunbar.

“The interesting question is whether this is some kind of organic effect or whether this is a cumulative ‘playground effect’,” he says. “Because you never quite catch up if you start small, so all your life you find yourself at the bottom of the social pile. One could imagine that this might give rise to suicidal tendencies eventually.”

Journal reference:

Mental Health – Discover the latest research in our continuously updated special report.

Many “sugar-free” products such as chewing gum and sweets contain a sweetener called sorbitol. It is a sugar alcohol with around a third fewer calories than sucrose, or table sugar.

However, the substance can have laxative effects if taken in large enough amounts – a fact that many people are unaware of because potential side-effects are usually listed in small print on the packaging, say the researchers.

The warning comes after Herbert Lochs, a gastroenterologist at in Berlin, Germany, and colleagues were referred two cases of patients with excessive diarrhoea and weight loss. Both had been investigated extensively by other doctors who could find no cause for their conditions.

After numerous tests with the first patient, a 21-year-old woman, Lochs measured her stool electrolytes. It appeared that something in the gut was drawing out large amounts of water, which led to the weight loss and diarrhoea. She had up to 12 episodes of diarrhoea a day.

Quick recovery

When questioned about her diet, the woman admitted to chewing large amounts of gum every day. Each stick contains about 1.25g of sorbitol. The team worked out she was exposing herself to 18-20g of sorbitol per day.

The second patient, a 46 year old man, told the team he chewed 20 sticks of gum a day and ate up to 200g of sweets – a consumption of 30g of sorbitol daily.

Only relatively small amounts of sorbitol (5 to 20g) are needed to cause gastrointestinal symptoms such as stomach cramps, bloating and gas. Higher doses (20-50g) are linked to malabsorption of nutrients, malnutrition, and substantial weight loss.

When both patients began a sorbitol-free diet, their diarrhoea went away and both gained weight. This was not before significant cost to the health service though, notes Professor Lochs.

Diabetic warning

“This could have saved a lot of money if it had been found earlier on,” he says. The study highlights the importance of examining a patient’s diet in cases of unexplained weight loss.

Sorbitol is put into many dietetic products for diabetics as an alternative to glucose, adds Lochs. He says that sorbitol might sometimes add to bowel problems, which are associated with diabetes.

points out it does not recommend “diabetic” foods to people with the condition.

“Sorbital is often used in foods labelled ‘diabetic’ such as chocolates, sweets, and biscuits. As these foods tend to be ‘treat’ foods and have no sugar some people may think that it’s fine to eat large quantities,” notes Jemma Edwards, a dietitian for the charity.

“We don’t recommend these foods because there are no added nutritional benefits and they are often more expensive.”

Journal reference:

The rising prevalence of these strains was found in Australia, New Zealand, England, Scotland and Denmark. The findings should prompt clinics to change practice and use at least two tests that work in different ways to detect the infection, the scientists say.

The prolyliminopeptidase (PIP) enzyme was previously thought to be present in all strains of gonorrhoea and was therefore used in many diagnostic tests. However, mutations or deletions in the PIP gene that prevent the production of this enzyme had been identified in some strains. Gonorrhoea is known for its ability to mutate throughout its entire growth phase.

Magnus Unemo, a microbiologist at Orebro University Hospital, Sweden and colleagues examined a total of 41 samples lacking the PIP enzyme from patients in Australia, New Zealand and Scotland. The samples were obtained between 2001 and 2004.

To see how widespread this stealth strain is across the globe, they then compared these with samples from other studies in England and Denmark.

Widespread dissemination

All the samples from New Zealand and Scotland, and 83% of Australian samples, were indistinguishable or very similar to the English and Danish samples and had evolved from a single original strain. The data show “widespread dissemination” of the strain, the researchers say.

The strain was previously known to be circulating among homosexual men, but the new work suggests it has become a growing concern within the heterosexual population as well.

The strain did not appear resistant to the antibiotics typically used to treat gonorrhoea and all patients were given treatment.

Untreated gonorrhoea infections can cause severe and permanent health problems and can even be fatal. It can also cause infertility by harming the testicles or fallopian tubes. These risks mean it is “crucial that a rapid, highly sensitive and specific confirmation of N. gonorrhoeae is provided,” the authors say.

Journal reference: Sexually Transmitted Infections (vol 83, p 47)

Dangerous oxygen starvation, or “fetal hypoxia”, currently takes time to detect so many doctors proceed to caesarean surgery rather than risk a child’s life. But such operations also carry health risks for the mothers.

Nick Dale, a neuroscientist at the University of Warwick, UK, decided to look a faster, more efficient test than the current practice of analysing the pH of the baby’s blood – a marker of hypoxia – in a blood-gas analyser.

Over 30 years’ worth of research has shown that the chemical hypoxanthine is a marker for hypoxia, so he developed a biosensor to measure blood hypoxanthine levels. The biosensor showed good accuracy in tests using horse blood and now his team is designing a prototype to be tested by doctors and midwives in preliminary human trials in five UK hospitals.

Two-minute test

The team plans to use fetal blood left over from the current pH test sample – taken from the unborn infant’s scalp using a scalpel introduced via a tube into the mother’s vagina. Researchers will compare the prototype sensor’s performance with that of the blood-gas analyser.

“Sometimes the blood-gas analyser does not accept the sample – for example if there is an air bubble in it – so then you need to get another. You can imagine quite a lot of critical time could go by before you get a result,” says Dale. “With our test you get a result in a maximum of 2 minutes.”

The biosensor works by using an enzymatic reaction to produce a signal in proportion to the amount of hypoxanthine present in a sample. The team hopes to be ready for the human trials in 18 to 24 months, working with a company called Sarissa Biomedical Ltd.

Everybody gains

If widely adopted, the biosensor could lead to a decrease in the number of unnecessary caesareans, Dale hopes. About 23% of 575,900 live births in England were caesareans in 2003 – with more than half of those done as emergencies, according to the UK’s department of health.

“In some units the c-section rate is approaching 30%,” notes Dale, “and it shouldn’t be more than half that, really. If we could get that rate down, everyone would gain and there would be a tremendous economic benefit too.”

Dale hopes the new biosensor could eventually be used as a continuous monitor for hypoxia by attaching it to the unborn baby’s scalp.

With bird flu’s 50% mortality rate in humans, the possibility of resistance to antiviral treatments, no developed human vaccines and the spread bird flu across the globe, new thinking and treatments are urgently needed, argues a team from the Karolinska University Hospital in Stockholm, Sweden.

Their reasoning has been published by The Lancet – just 10 days after submission – to get the suggestion out to the scientific community as speedily as possible.

Jan-Inge Henter, a paediatric clinical oncologist, noticed that the symptoms of patients infected with H5N1 were very similar to those with an often fatal immune disease called haemophagocytic lymphohitiocytosis (HLH). Indeed, three papers on patients with H5N1 note its symptoms include a profound over-response of the immune system, which also occurs in HLH patients.

The over-production of certain immune messengers, such as interleukin 6, is seen in H5N1 patients and cause of death is often linked to sepsis with multi-organ failure – all symptoms also seen with HLH.

Programmed cell death

But HLH, both in its inherited form and in response to Epstein-Barr virus, can be treated with a cocktail of drugs including a key chemotherapy called etoposide, which kills excess immune cells. When the chemotherapy is given immediately, the treatments increased survival rates from 56% to 90% in comparison with giving treatment at four weeks or not at all, according to one retrospective study of patients with Epstein-Barr-virus-associated HLH.

“Etoposide is an excellent trigger of programmed cell death [in immune cells],” explains Henter.

“So our thinking is that these patients with severe [H5N1] infection, their immune regulation is out of control. We are down-regulating things to kill off some of the cells, to get some kind of balance – there is some logic to how this could work.”

Henter is calling on the World Health Organization to recommend scientists conduct research around the hypothesis. He suggests this work could bypass animal models and move directly to patients with H5N1 that have secondary HLH.

Balance of risk

“Etoposide is licensed for this indication, it is well known. The treatment protocol has been used successfully in humans affected by severe virus infections for more than 10 years,” Henter told 91av. He adds that the drug is widely available and inexpensive.

He concedes it might carry risks for dangerously ill individuals, but points out that people with virus-associated HLH are already at high risk of death if left untreated.

The WHO has yet to formally respond but Nikki Shindo, who leads the WHO’s clinical group on H5N1 told 91av that doctors at Yuzuncu Yil University in Turkey debated the use of similar drug regimens when dealing with H5N1 patients from the recent bird flu outbreak there.

At the end of March, the WHO is inviting clinicians from all countries with human cases of H5N1 to discuss the best treatment options.

Journal reference: The Lancet (DOI: 10.1016/SO140-6736(06)68232-9)

Crohn’s disease is a long term, inflammatory condition that leads to holes and ulcers in the small and large intestines and can severely impact on sufferers’ quality of life. Its cause has remained a mystery but current thinking is that it is an autoimmune disorder; where the body attacks its own tissues.

But a team from University College London, UK, wondered if the disorder might be due to an under reaction of the immune system instead.

A lack of an acute inflammatory response might lead to the delay or incomplete removal of bacteria and other bowel contents from the gut characterised by Crohn’s. This material then breaches the mucosal barrier, and its continued presence might provoke a huge immune reaction and secondary chronic inflammation, the researchers reasoned.

White blood cells

The team compared patients with Crohn’s disease with matched healthy controls. They took a sample from the rectums of nine controls and six patients to see the gut’s reaction to the scraping.

The mucosa (or membrane) was normal in all patients at the start, but six hours after the biopsy, healthy controls had an acute inflammatory response but the patients with Crohn’s did not. They produced much lower amounts of white blood cells and inflammatory mediators – with a 79% reduction in immune cells called neutrophils and a 63% reduction in interleukin 8-positive cells, in comparison with controls. Research on the small intestine gave a similar result.

To check whether the response was just confined to the gut, the team did another experiment using sandpaper to breach the skin barrier. Five hours after this trauma, 13 Crohn’s patients still had much lower numbers of neutrophils and interleukin 8 cells at the trauma site than controls.

Dead E. coli

Further experiments injecting heat-killed Escherichia coli into the skin on the forearm lead to a nine-fold increase in blood flow to the trauma site in healthy controls 24 hours later, but not in the 12 Crohn’s patients tested.

“In Crohn’s patients this was grossly defective,” Anthony Segal, who led the study, told 91av. The researchers then tested Viagra (sildenafil) to see its effect on blood flow.

“This resulted in marked increases in blood flow in all patients so it might be helpful in treatment of Crohn’s, particularly in the colon,” says Segal. He says his team are the first to trial use of Viagra for patients with Crohn’s disease. The study was self-funded, he notes.

Journal reference: The Lancet (vol 367 p 668)

Michael Morales was to be put to death for the rape and murder of a 17-year-old girl in 1981. He has gone back to death row with his execution postponed indefinitely, after medical professionals – under directions from a federal judge who intervened in the case – refused to participate in the execution.

Morales’ lawyers had successfully argued that the doctors should be present to ensure that Morales was unconscious whilst he was being executed. However, although the judge agreed to this, the two anaesthesiologists involved refused to monitor the injection of a three-drug cocktail – the accepted form of lethal injection given in the vast majority of the 38 US states with the death penalty.

When they refused, US district judge Jeremy Fogel ruled that only the drug sodium pentothal should be used to kill him. It would have to be administered by a licensed professional and injected directly in Morales’ vein. Normally an intravenous tube inserted into the death chamber delivers the drugs into the offender.

Do no harm

Under Californian law, the sedative sodium pentothal can only be administered by certain health professionals. Prison officials could not find any professionals willing to do this and the State then rejected the judge’s conditions.

Officials say they will ask the judge’s permission to reinstate use of the usual three-drug-cocktail procedure. This involves giving sodium pentothal for anaesthesia then pancuronium bromide to relax muscles and potassium chloride to stop the heart. A hearing on this will be held in May 2006.

The American Medical Association has opposed the conditions suggested by Judge Fogel, saying that involvement of a doctor in execution in such a way goes against its code of medical ethics and the Hippocratic Oath, which states: “First, do no harm.”

Question of pain

Doctors can participate in executions, the AMA points out, but only in certain parts of the procedure, such as administering tranquillisers, monitoring vital signs, observation and technical advice.

The California Medical Association has said it would sponsor a Bill under state law to make it illegal for clinicians to participate in executions. “We believe physician involvement in capital punishment at any level is unethical,” says Michael Sexton, an emergency physician in Marin County and president of the association, speaking to the San Francisco Chronicle.

In fact, executions are rarely carried out by skilled or medical practitioners, the author of a study in the Lancet (vol 365, p1412) told 91av. Leonidas Koniaris, a surgeon in Miami whose research calls into question whether lethal injections are always painless. He said the injections were usually done by unskilled individuals and unmonitored.

Conclusions questioned

Koniaris suggested that 43 of the 49 executed prisoners in his study had lower levels of sodium thiopental than would be required during typical hospital surgery, and that 21 subjects might have been conscious – but unable to move due to the injection of muscle relaxant – when potassium chloride was injected.

But his findings have been questioned by other scientists who say post-mortem drug concentrations are difficult to interpret and that times between autopsy and blood sampling can influence findings.

Mark Heath at Columbia University in New York, US, and colleagues writing in the Lancet (vol 366, p 1073) say the data does not justify the conclusion “that so large a proportion of inmates have experienced awareness during lethal injection. Indeed, published and unpublished data, and clinical experience, contradict their conclusions”.